Inspection device

ABSTRACT

An inspection device ( 1 ) has a particle detector ( 3 ) adapted to detect particles ( 5 ) in a liquid, a seat ( 6 ) adapted to position a container ( 4 ) housing the liquid in an area of operation ( 311 ) of the particle detector ( 3 ) and a vibration arrangement ( 2 ) for vibrating the container ( 4 ). The vibration arrangement ( 2 ) comprises a frequency generator ( 21 ) adapted to provide an electrical signal and a transducer ( 22 ) adapted to transduce the electrical signal provided by the frequency generator ( 21 ) into an acoustic wave ( 221 ). The seat ( 6 ) is adapted to position the container ( 4 ) adjacent to the transducer ( 22 ). for inspecting a liquid inside a container ( 4 ) with respect to the existence of particles ( 5 ). The inspection device ( 1 ) allows for an accurate and gentle inspection of the liquid filled in the container and for detecting particles in the liquid.

TECHNICAL FIELD

The present invention relates to an inspection device according to thepreamble of independent claim 1. Such inspection devices having aparticle detector adapted to detect particles in a liquid, a seatarranged to position a container in an area of operation of the particledetector, and a vibration arrangement for vibrating the container can beused for inspecting the liquid inside the container with respect to theexistence of particles.

BACKGROUND ART

Many types of liquids such as parenterals or other liquid drugs,nutritions or beverages are frequently controlled for the absence offoreign particulates before they are further processed. For example,liquid drugs have to be fully inspected for the absence of particlesbefore being introduced to the market. The inspection process istypically a visual or optoelectrical inspection by trained humans, aninspection system or a combination of both.

For allowing an accurate detection of foreign particulates in theliquid, usually a mobilization of particles is part of the inspectionprocess. This mobilization process makes sure that particles can bedetected in the liquid, even though they are on the base of thecontainer, stuck at the container walls or floating on the surface ofthe liquid that is to be inspected. For mobilization it is known toshake, vibrate or rotate the container for moving the foreign particles.For example, U.S. Pat. No. 8,576,279 B2 describes an inspection systemfor detecting foreign bodies in a beverage wherein the beverage bottleis vibrated within the inspection process.

However, such mobilization can lead to several problems during theinspection process. For example, it can introduce air bubbles into theproduct that disturb the inspection process by hiding floating particlesor mimicking particles in the liquid. Or, it can transport particlesthat are in the liquid to the surface of container closure systems wherethey can get stuck because of adhesion forces or electrostatic effectsand afterwards they are harder to detect especially for optoelectricaldetectors. And last but not least, any form of normal shaking or usualpre-rotation typically is not compatible with an inspection of liquidproduct in an open or partially open container. This can be particularlyimportant in connection with chemical or biological pharmaceuticalliquids which have to be dried such as freeze dried. If a drying processfollows the inspection, the container usually is still open to allow forsublimation or evaporation during the drying process. Shaking orpre-rotation can lead to spill of product and potential product residuein the area of the container closure system, potentially leading tofailed Container Closure Integrity (CCI). Furthermore, it needs to beavoided that product gets in contact with the primary container abovethe normal fill level. If the area above the fill level is in contactwith product and a drying process follows, product residues can dry atthe wall of the container which can lead to cosmetic or criticaldefects.

Therefore, there is a need for a device or system allowing an accurateand gentle inspection of a liquid filled in a container for detectingparticles in the liquid such as, for example, for detecting particles ina liquid before a freeze-drying step in a pharmaceutical preparationprocess.

DISCLOSURE OF THE INVENTION

According to the invention this need is settled by an inspection deviceas it is defined by the features of independent claim 1. Preferredembodiments are subject of the dependent claims.

In particular, the invention deals with an inspection device forinspecting a liquid inside a container with respect to the existence ofparticles. The inspection device comprises a particle detector adaptedto detect particles in the liquid inside the container, a seat arrangedto position the container in an area of operation of the particledetector, and a vibration arrangement for vibrating the container. Thevibration arrangement comprises a frequency generator to provide anelectrical signal and a transducer adapted to transduce the electricalsignal provided by the frequency generator into an acoustic wave. Theseat is arranged to position the container adjacent to the transducer.

The term “liquid” as used herein can relate to any flowable substancesuch as a liquid drug, a nutrition, a beverage or the like. It canparticularly relate to a chemical, biochemical, biological orpharmaceutical substance, e.g., intended for being lyophilized.

The term “particles” in connection with the liquid inside the containercan relate to any bodies or solid particulates being present in theliquid. Such particles can, e.g., comprise fibers or particles intrinsicto the liquid. They can further comprise foreign bodies such as glass,e.g., originating from the container or metal, e.g., originating from acap of the container.

The term “adjacent” with regard to the container and the transducer canrelate to a position allowing the acoustic wave to vibrate the containerand particularly the liquid inside the container. Thereby, adjacent doesnot exclude anything other being arranged between the transducer and thecontainer as long as acoustic waves of sufficient intensity or qualitycan be transferred to the container or liquid. Advantageously, thecontainer is adjacent to the transducer such that the acoustic waves canessentially unhinderedly travel from the transducer to the container orliquid.

The frequency generator can be an electronic apparatus connected to thetransducer, e.g., via a cable or the like. It can be equipped with aregulator for adjusting the frequency to be provided and a display forindicating the adjusted frequency. The frequency generator can furtherhave a power wire which is connected to an electric energy source, e.g.,via a plug or a similar connector.

The seat can have a structure for holding or supporting the containerwhich is adapted to the shape and form of the container. For manycontainers having a flat bottom such as, e.g., vials the seat can have ahorizontal plane surface onto which the container can be placed.

The inspection device allows for applying a high frequency and lowamplitude shaking to the container. By such vibration of the containerparticles being present in the container can efficiently be mobilized ordispersed in the liquid inside the container such that they canefficiently be identified or traced. In particular, it allows foressentially mobilizing the particles whereas the liquid can be keptcomparably calm. This makes a comparably fast and accurate inspectionpossible as well as a prevention or at least reduction of air bubbleproduction in the liquid, an improved immobilization of floating orgrounded particles, a prevention of disposition of particles on thecontainer closure systems and a comparably efficient implementation in achemical or pharmaceutical preparation process including freeze drying.

Thus, the inspection device according to the invention allows for anaccurate and gentle inspection of the liquid filled in the container andfor detecting particles in the liquid. The inspection device can beparticularly suitable for detecting particles in liquids before afreeze-drying step in a pharmaceutical preparation process where acomparably high precision and reliability is to be achieved.

Preferably, the acoustic wave is an ultrasonic acoustic wave. Moreparticularly, the transducer can be adapted to transduce the electricalsignal provided by the frequency generator into an ultrasonic acousticwave. Such ultrasonic waves at appropriate frequencies allow for aparticularly efficient and suitable inspection.

The inspection of the liquid can particularly be an optoelectronic oroptical (visual) inspection. Thereby, the particle detector preferablycomprises a camera. When using a camera, the area of operation of theparticle detector can be defined by the field of view of the camera. Inparticular, the camera can be positioned such that a transparent sectionof the container is in its field of view which allows for an efficientinspection through the transparent section.

For increasing efficiency of the inspection, the particle detector canfurther comprise one or plural light sources. Such light sources mayefficiently illuminate the container and its interior and thereby theliquid. For example, the light source of the particle detector can bearranged below the seat such that, in use, it is located below thecontainer. Like this, the illumination can be provided through thebottom of the container which has been shown to be particularlyefficient. Also, for optimizing the inspection of the container and foroptimizing the equipment design the particle detector can comprise oneor more mirrors guiding the optical detection and/or illumination.

The transducer of the vibration arrangement preferably is apiezoelectric transducer. Such a piezoelectric transducer allows forefficiently providing ultrasonic waves thereby inducing comparably fast(high frequency) vibrations to a comparably low extent (low amplitude).The transducer can have any shape suitable for its intended application.For example, it can be cuboid, cylindrical, cuboid with a cylindricalhole, cylindrical with a cylindrical hole, ring-shaped,ring-sector-shaped, any combination thereof or the like. In particular,the shape of the transducer can be adapted to optimize the transfer ofthe acoustic wave to the container.

Preferably, the vibration arrangement comprises a further transduceradapted to transduce a further electrical signal into a further acousticwave, the seat is arranged to position the container adjacent to thefurther transducer, the acoustic wave generated by the transducer of thevibration arrangement has a first frequency, and the further acousticwave generated by the further transducer of the vibration arrangementhas a second frequency different from the first frequency.

Having plural transducers allows for a more complete vibration of theliquid or container. Furthermore, it allows for providing varyingvibration movements which makes it possible to efficiently mobilizeparticles of varying sizes, shapes and consistence.

The further electrical signal can be provided by a further frequencygenerator. However, preferably, the frequency generator of the vibrationarrangement is adapted to provide the further electrical signal to thefurther transducer. Such a frequency generator providing both, theelectrical signal as well as the further electrical signal allows for anefficient implementation of the inspection device. The frequencygenerator can be equipped with means for adjusting the single electricalsignals independently.

The first frequency preferably is in a range of about 0.5 MHz to about 2MHz. Such a comparably high frequency can be particularly suitable formobilizing fibers and intrinsic particles. The second frequencypreferably is in a range of about 20 kHz to about 50 kHz. Such lowerfrequency allows to form standing waves in the liquid due to theirreflection at the liquid surface. Standing waves are efficient formoving comparably heavy particles such as, e.g., glass or metal.Particularly efficient might be to apply comparably high frequencies bythe transducer at a side wall portion of the container and to applycomparably low frequencies by the further transducer at the bottom ofthe container. This allows for an efficient, fast and completemobilization of different kind of particles in the liquid which can thenbe identified.

Preferably, the container has a side wall portion and a bottom portionand the seat is arranged to position the side wall portion of thecontainer adjacent to the transducer of the vibration arrangement andthe bottom portion of the container adjacent to the further transducerof the vibration arrangement. Such an arrangement allows for anefficient operation of the first and second transducers particularlyallowing an accurate provision of different waves.

Preferably, the electrical signal is a pulsed electrical signal and theacoustic wave transduced by the transducer of the vibration arrangementis a pulsed acoustic wave. Similarly, the further electrical signalpreferably is a pulsed electrical signal and the further acoustic wavetransduced by the further transducer of the vibration arrangementpreferably is a pulsed acoustic wave. Such pulsed electrical signals andacoustic waves allow for minimizing the amount of energy introduced intothe liquid which might avoid the risk of damaging the liquid, e.g.,being a drug product. Thereby, the transducer of the vibrationarrangement and the further transducer of the vibration arrangementpreferably are arranged to intermittently provide the acoustic wave andthe further acoustic wave to the container.

Preferably, the particle detector is arranged to laterally observe thecontainer. Compared to observing the container from other sides such asthrough the bottom, laterally observing the container can allow for aninterference-free monitoring of the liquid. Thereby, particles in theliquid can be identified in a comparably reliable and efficient manner.

The term “container” as used herein can relate to any reservoir suitablefor storing and transporting a liquid. Where the liquids are medicamentsor the like, the container preferably is a vial. Thereby, the term“vial” can relate to any vial in the literal sense, i.e. a comparablysmall vessel or bottle, often used to store pharmaceutical products orpharmaceuticals or medications in liquid, powdered or capsuled form. Thevial can be made of a sterilizable material such as glass or plasticsuch as, e.g., polypropylene.

Preferably, the inspection device comprises a conveying unit adapted tomove the container along the transducer of the vibration arrangement.The conveyor unit can move the complete seat together with the containerto pass the vibration arrangement or it can move the container along theseat. It can for example comprise a moving belt onto which the containeris arranged. Or it can comprise plural moving belts between which thecontainer is clamped to be forwarded. Such a conveying unit allows forefficiently processing containers in an automated manner which makes anefficient inspection on an industrial scale possible.

BRIEF DESCRIPTION OF THE DRAWINGS

The inspection device according to the invention is described in moredetail herein below by way of an exemplary embodiment and with referenceto FIG. 1 which shows a schematic view of an embodiment of theinspection device according to the invention.

DESCRIPTION OF EMBODIMENTS

In the following description certain terms may be used for reasons ofconvenience and are not intended to limit the invention. The terms“right”, “left”, “up”, “down”, “under” and “above” refer to directionsin the FIGURE. The terminology comprises the explicitly mentioned termsas well as their derivations and terms with a similar meaning. Also,spatially relative terms, such as “beneath”, “below”, “lower”, “above”,“upper”, “proximal”, “distal”, and the like, may be used to describe oneelement's or feature's relationship to another element or feature asillustrated in the FIGURES. These spatially relative terms are intendedto encompass different positions and orientations of the devices in useor operation in addition to the position and orientation shown in theFIGURES. For example, if a device in the FIGURES is turned over,elements described as “below” or “beneath” other elements or featureswould then be “above” or “over” the other elements or features. Thus,the exemplary term “below” can encompass both positions and orientationsof above and below. The devices may be otherwise oriented (rotated 90degrees or at other orientations), and the spatially relativedescriptors used herein interpreted accordingly. Likewise, descriptionsof movement along and around various axes includes various specialdevice positions and orientations.

To avoid repetition in the FIGURE and the descriptions of the variousaspects and illustrative embodiments, it should be understood that manyfeatures are common to many aspects and embodiments. Omission of anaspect from a description or FIGURE does not imply that the aspect ismissing from embodiments that incorporate that aspect. Instead, theaspect may have been omitted for clarity and to avoid prolixdescription.

FIG. 1 shows an embodiment of the inspection device 1 according to theinvention which comprises a seat 6, a particle detector 3 and avibration arrangement 2. The seat 6 has a horizontal top surface ontowhich a vial 4 as a container is placed. The vial 4 has an essentiallycylindrical glass body with a sidewall 41, a bottom 43 and a neck 42.The neck 42 of the body has an open top end which is loosely closed by alyophilisation stopper 44. The body of the vial 4 houses a liquid drugproduct 7 which is intended to be lyophilized. The liquid 7 has aspecific fill level 71.

The particle detector 3 is positioned besides the vial 4. It is equippedwith a camera 31. The camera 31 is arranged and adjusted such that theside wall 41 of the vial 4 is in its field of view 311. Thereby, thecamera 31 laterally observes the vial 4 and the liquid 7 inside the vial4.

The vibration arrangement 2 comprises a frequency generator 21, apiezoelectric transducer 22 and a piezoelectric further transducer 23.The frequency generator 21 has four slots 211 one of which beingconnected to the transducer 22 via a first cable 222 and another one ofwhich being connected to the further transducer 23 via a second cable232. Above each slot 211 the frequency generator 21 has a controller214. Each controller 214 is associated to one of the slots 211 in orderto adjust an electric signal provided via the slot 211. The frequencygenerator 21 is further equipped with a power switch 213 and displays212 showing parameters adjusted.

The transducer 22 is arranged besides the vial 22 such that it ispositioned laterally adjacent to the side wall 41 of the vial 4. Thefurther transducer 23 is arranged below the vial 22 such that it ispositioned underneath adjacent to the bottom 43 of the vial 4. Thefrequency generator 21 provides a first pulsed electric signal to thetransducer 22 via the first cable 222. This first electric signal isadjusted such that it is transduced by the transducer 22 into firstultrasonic waves 221 having a frequency in a range from about 0.5 MHz toabout 2 MHz. Similarly, the frequency generator 21 provides a secondpulsed electric signal to the further transducer 23 via the second cable232. The second electric signal is adjusted such that it is transducedby the further transducer 23 into further or second ultrasonic waves 231having a frequency in a range from about 20 kHz to about 50 kHz.

The transducer 22 provides the first waves 221 from right to left viathe sidewall 41 into the liquid 7 inside the vial 4. Due to thecomparably high frequency of the first waves 221, they do primarilymobilize fibres and intrinsic particles 5 in the liquid 7. In additionto that, the further transducer 23 provides the second waves 231 bottomup via the bottom 43 into the liquid 7 inside the vial 4. Due toreflection at a top surface of the liquid 7 the comparably low frequencysecond waves form standing waves which are primarily able to movecomparably heavy particles 5. By means of the particle detector 3 themobilized particles 5 can efficiently be detected in an accurate andgentle manner.

This description and the accompanying drawing that illustrate aspectsand embodiments of the present invention should not be taken aslimiting—the claims defining the protected invention. In other words,while the invention has been illustrated and described in detail in thedrawing and foregoing description, such illustration and description areto be considered illustrative or exemplary and not restrictive. Variousmechanical, compositional, structural, electrical, and operationalchanges may be made without departing from the spirit and scope of thisdescription and the claims. In some instances, well-known circuits,structures and techniques have not been shown in detail in order not toobscure the invention. Thus, it will be understood that changes andmodifications may be made by those of ordinary skill within the scopeand spirit of the following claims. In particular, the present inventioncovers further embodiments with any combination of features fromdifferent embodiments described above and below.

The disclosure also covers all further features shown in the FIGUREindividually although they may not have been described in the afore orfollowing description. Also, single alternatives of the embodimentsdescribed in the figures and the description and single alternatives offeatures thereof can be disclaimed from the subject matter of theinvention or from disclosed subject matter. The disclosure comprisessubject matter consisting of the features defined in the claims or theexemplary embodiments as well as subject matter comprising saidfeatures.

Furthermore, in the claims the word “comprising” does not exclude otherelements or steps, and the indefinite article “a” or “an” does notexclude a plurality. A single unit or step may fulfil the functions ofseveral features recited in the claims. The mere fact that certainmeasures are recited in mutually different dependent claims does notindicate that a combination of these measures cannot be used toadvantage. The terms “essentially”, “about”, “approximately” and thelike in connection with an attribute or a value particularly also defineexactly the attribute or exactly the value, respectively. The term“about” in the context of a given numerate value or range refers to avalue or range that is, e.g., within 20%, within 10%, within 5%, orwithin 2% of the given value or range. Components described as coupledor connected may be electrically or mechanically directly coupled, orthey may be indirectly coupled via one or more intermediate components.Any reference signs in the claims should not be construed as limitingthe scope.

1. An inspection device for inspecting a liquid inside a container withrespect to the existence of particles comprising: a particle detectoradapted to detect particles inside the liquid; a seat arranged toposition the container in an area of operation of the particle detector;and a vibration arrangement for vibrating the container, wherein thevibration arrangement comprises a frequency generator to provide anelectrical signal, and a transducer adapted to transduce the electricalsignal provided by the frequency generator into an acoustic wave havinga first frequency, a further transducer adapted to transduce a furtherelectrical signal into a further acoustic wave having a second frequencydifferent from the first frequency, wherein the container has a sidewall portion and a bottom portion, and the seat is arranged to positionthe side wall portion of the container adjacent to the transducer of thevibration arrangement and the bottom portion of the container adjacentto the further transducer of the vibration arrangement, wherein theparticle detector is disposed adjacent to the side wall portion of thecontainer and arranged to laterally observe the container, and whereinthe application of the first frequency applied at the side wall portionof the container and the second frequency applied at the bottom portionof the container allows for mobilization of different kinds of particlesin the liquid which can then be identified.
 2. The inspection deviceaccording to claim 1, wherein the acoustic wave is an ultrasonicacoustic wave.
 3. The inspection device according to claim 1, whereinthe particle detector comprises a camera.
 4. The inspection deviceaccording to claim 1, wherein the transducer of the vibrationarrangement is a piezoelectric transducer.
 5. (canceled)
 6. (canceled)7. The inspection device according to claim 1, wherein the firstfrequency is in a range of about 0.5 MHz to about 2 MHz.
 8. Theinspection device according to claim 7, wherein the second frequency isin a range of about 20 kHz to about 50 kHz.
 9. (canceled)
 10. Theinspection device according to claim 1, wherein the electrical signal isa pulsed electrical signal and the acoustic wave transduced by thetransducer of the vibration arrangement is a pulsed acoustic wave. 11.The inspection device according to claim 10, wherein the furtherelectrical signal is a pulsed electrical signal and the further acousticwave transduced by the further transducer of the vibration arrangementis a pulsed acoustic wave.
 12. The inspection device according to claim1, wherein the transducer of the vibration arrangement and the furthertransducer of the vibration arrangement are arranged to intermittentlyprovide the acoustic wave and the further acoustic wave to thecontainer.
 13. (canceled)
 14. The inspection device according to claim1, wherein the container is a vial.
 15. (canceled)
 16. The inspectiondevice according to claim 1, wherein the first frequency is higher thanthe second frequency.
 17. The inspection device according to claim 1,wherein the first frequency is configured for mobilizing fibers andintrinsic particles in the liquid.
 18. The inspection device accordingto claim 1, wherein the second frequency is configured for moving heavyparticles in the liquid.
 19. The inspection device according to claim 1,wherein the first frequency and the second frequency are configured formobilizing or dispersing the particles in the liquid inside thecontainer while the liquid is kept calm.
 20. The inspection deviceaccording to claim 3, wherein the camera is arranged such that atransparent section of the container is in a field view of the camera inorder to laterally observe the container and the liquid inside thecontainer.
 21. The inspection device according to claim 3, wherein thecamera is positioned, in a vertical direction above the transducer,which is positioned adjacent the side wall portion of the container.